Process for producing biaryl compound

ABSTRACT

A process for producing a biaryl compound, characterized by reacting an arylhydrazine compound, hydrogen peroxide and an aryl compound. When the reaction is conducted in the presence of a given metal or a compound of the metal or in the presence of a metal oxide obtained by reacting the given metal or a compound of the metal with hydrogen peroxide, then the yield of the biaryl compound is improved.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a Divisional of allowed U.S. application Ser. No. 10/502,619,filed Jul. 27, 2004, Now U.S. Pat. No. 7,554,000 which is the U.S.National Phase of International Application No. PCT/JP03/00245 filedJan. 15, 2003 and claims priority on Japanese Applications No.2002-27907, No. 2002-061608, and No. 2002-258584, filed in Japan on Feb.5, 2002, Mar. 7, 2002, and Sep. 4, 2002, respectively. The entirecontents of all these applications is incorporated herein by reference.

TECHNICAL FIELD

The present invention relates to a process for producing a biarylcompound

BACKGROUND ART

A biaryl compound is an extremely important compound as various chemicalproducts and intermediates for synthesis of them. It is generally knownthat a biaryl compound can be produced by Suzuki coupling reaction usingaryl boric acid, a reaction using a nickel catalyst and a Grignardreagent, Ullmann reaction using aryl iodide, or the like (e.g.Comprehensive Organic Synthesis, 3, 499(1991) etc.). However, all thesemethods use an expensive reagent, ligand or catalyst and, therefore,further improvement has been desired from an industrial point of view.

On the other hand, as a process for producing a biaryl compound withoutan expensive reagent, ligand or catalyst such as the above-mentionedreagent, ligand or catalyst, there was proposed a method comprisingreaction of an arylhydrazine compound, an oxidizing agent and an arylcompound. For example, methods using, as an oxidizing agent, (1) silveroxide (J. Chem. Soc., 2512 (1957)), (2) manganese acetate (J. Chem. Soc.Perkin Trans. 1, 3042(2001)), (3) mercury oxide (Liebigs Ann. Chem.,199, 332(1879)), (4) barium ferrate (Bull. Chem. Soc. Jpn., 61,2185(1988)), (5) lead acetate (J. Chem. Soc. (C), 1663(1969)) and (6)potassium superoxide (Aust. J. Chem., 37, 2499 (1984)) respectively werereported. However, all the above-mentioned oxidizing agents arerelatively expensive and moreover, may be toxic or be difficult tohandle after reaction. Therefore, development of an industrially moreadvantageous method has been desired.

DISCLOSURE OF THE INVENTION

Under such circumstances, the present inventor intensively studied aprocess of industrially and more advantageously producing a biarylcompound and as a result, found that a biaryl compound can be producedfrom an arylhydrazine compound or an arylhydrazine compound and an arylcompound by using hydrogen peroxide, which is inexpensive, easy to useand converted into harmless water after reaction, that is, a clean andexcellent oxidizing agent. Further, the present inventor found that theyield of a biaryl compound can be improved by performing the reaction inthe presence of at least one species selected from the group consistingof the following groups (A) and (B):

(A) a Group Va element metal or a compound thereof, a Group VIa elementmetal or a compound thereof, a Group VIIa element metal or a compoundthereof and a Group VIIIa element metal or a compound thereof,

(B) a Group Va element metal oxide, a Group VIa element metal oxide, aGroup VIIa element metal oxide and a Group VIIIa element metal oxideobtained by reacting the metal or the metal compound of the group (A)with hydrogen peroxide, and finally completed the present invention.

That is, the present invention provides:

(1) a process for producing a biaryl compound, which comprises reactingan arylhydrazine compound, hydrogen peroxide and an aryl compound,

(2) a process for producing a biaryl compound, wherein the reaction asdescribed in the above (1) is performed in the presence of at least onespecies selected from the group consisting of the following groups (A)and (B):

(A) a Group Va element metal or a compound thereof, a Group VIa elementmetal or a compound thereof, a Group VIIa element metal or a compoundthereof and a Group VIIIa element metal or a compound thereof,

(B) a Group Va element metal oxide, a Group VIa element metal oxide, aGroup VIIa element metal oxide and a Group VIIIa element metal oxideobtained by reacting the metal or the metal compound of the group (A)with hydrogen peroxide,

(3) a process for producing a biaryl compound, which comprises reactingan arylhydrazine compound with hydrogen peroxide, and

(4) a process for producing a biaryl compound, wherein the reaction asdescribed in the above (3) is performed in the presence of at least onespecies selected from the group consisting of the above-mentioned groups(A) and (B).

MODE FOR CARRYING OUT THE INVENTION

First, a process for producing a biaryl compound by reacting anarylhydrazine compound, hydrogen peroxide and an aryl compound, and amethod of performing the aforementioned reaction in the presence of atleast one selected from the group consisting of the aforementionedgroups (A) and (B) will be explained.

The arylhydrazine compound may be a compound in which at least onehydrazino group is bound to an aromatic ring (e.g. a benzene ring or anaphthalene ring), a heteroaromatic ring (e.g. a pyridine ring, athiazole ring or an oxazole ring) or a fused heteroaromatic ring (e.g.benzothiazole, benzoxazole, quinoline or isoquinoline). Thearylhydrazine compound may have a substituent other than a hydrazinogroup on the aromatic ring or the heteroaromatic ring.

Such arylhydrazine compound includes an arylhydrazine compoundrepresented by the formula (1):Ar—NHNH₂   (1)

wherein Ar represents an aromatic group such as a phenyl group or anaphthyl group, or a heteroaromatic group such as a pyridyl group, athiazolyl group or an oxazolyl group (e.g. benzothiazole, benzoxazole,quinoline, isoquinoline, etc.).

A substituent of the arylhydrazine compound (including the arylhydrazinecompound of the aforementioned formula (1)) will be explained below.

The substituent other than a hydrazino group includes a substituted orunsubstituted alkyl group, a substituted or unsubstituted alkoxy group,a substituted or unsubstituted alkoxycarbonyl group, a substituted orunsubstituted aryl group, a substituted or unsubstituted aryloxy group,a substituted or unsubstituted aryloxycarbonyl group, a substituted orunsubstituted aralkyl group, a substituted or unsubstituted aralkyloxygroup, a substituted or unsubstituted aralkyloxycarbonyl group, asubstituted or unsubstituted acyl group, a halogen atom, a carboxylgroup, a sulfo group (—SO₃H), a sulfonamido group, a sulfonic acid (arylor alkyl) ester group, a sulfonyl group, a cyano group, a hydroxylgroup, a nitro group, an amino group and an amido group.

Among these substituents, adjacent substituents may be taken together toform a part of a ring structure.

The halogen atom includes a fluorine atom, a chlorine atom and a bromineatom.

The alkyl group of the substituted or unsubstituted alkyl group, thesubstituted or unsubstituted alkoxy group, and the substituted orunsubstituted alkoxycarobonyl group includes straight, branched orcyclic alkyl groups having 1 to 20 carbon atoms, such as a methyl group,an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group,an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentylgroup, a n-hexyl group, a n-heptyl group, a n-octyl group, a n-nonylgroup, a n-decyl group, an undecyl group, a dodecyl group, a tridecylgroup, a tetradecyl group, a pentadecyl group, a hexadecyl group, aheptadecyl group, an octadecyl group, a nonadecyl group, an eicosylgroup, a cyclopropyl group, a 2,2-dimethylcyclopropyl group, acyclopentyl group, a cyclohexyl group or a menthyl group. In the presentinvention, unless otherwise indicated, an alkyl group has theaforementioned meaning.

The aryl group of the substituted or unsubstituted aryl group, thesubstituted or unsubstituted aryloxy group and the substituted orunsubstituted aryloxycarbonyl group includes a phenyl group, a naphthylgroup and a biphenyl group. In the present invention, unless otherwiseindicated, an aryl group has the aforementioned meaning.

The aralkyl group of the substituted or unsubstituted aralkyl group, thesubstituted or unsubstituted aralkyloxy group and the substituted orunsubstituted aralkyloxycarbonyl group includes groups formed by bindingof the aforementioned alkyl group and the aryl group. In the presentinvention, unless otherwise indicated, an aralkyl group has theaforementioned meaning.

The acyl group of the substituted or unsubstitued acyl group includesgroups formed by binding of the aforementioned alkyl group or aryl groupand a carbonyl group. In the present invention, unless otherwiseindicated, an acyl group has the aforementioned meaning.

The substituted alkyl group includes alkyl groups substituted withsubstituent(s) selected from an alkoxy group, an alkoxycarbonyl group,an aryloxy group, an aryloxycarbonyl group, an aralkyl group, anaralkyloxy group, an aralkyloxycarbonyl group, an acyl group, a halogenatom, a carboxyl group, a sulfo group (—SO₃H), a sulfonamido group, asulfonic acid (aryl or alkyl) ester group, a sulfonyl group, a cyanogroup, a hydroxyl group, a nitro group, a amino group and an amidogroup.

The substituted aryl group includes aryl groups substituted withsubstituent(s) selected from an alkoxy group, an alkoxycarbonyl group,an aryloxy group, an aryloxycarbonyl group, an aralkyl group, anaralkyloxy group, an aralkyloxycarbonyl group, an acyl group, a halogenatom, a carboxyl group, a sulfo group (—SO₃H), a sulfonamido group, asulfonic acid (aryl or alkyl) ester group, a sulfonyl group, a cyanogroup, a hydroxyl group, a nitro group, an amino group and an amidogroup.

The substituted aralkyl group includes aralkyl groups substituted withsubstituent(s) selected from an alkoxy group, an alkoxycarbonyl group,an aryloxy group, an aryloxycarbonyl group, an aralkyl group, anaralkyloxy group, an aralkyloxycarbonyl group, an acyl group, a halogenatom, a carboxyl group, a sulfo group (—SO₃H), a sulfonamido group, asulfonic acid (aryl or alkyl) ester group, a sulfonyl group, a cyanogroup, a hydroxyl group, a nitro group, an amino group and amido group.

The substituted alkyl group includes a bromomethyl group, a chloromethylgroup, a fluoromethyl group, a trifluoromethyl group, a methoxymethylgroup, an ethoxymethyl group, a methoxyethyl group and amethoxymethylcarbonyl group.

The alkoxy group specifically includes straight, branched or cyclicalkoxy groups having 1 to 20 carbon atoms, such as a methoxy group, anethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group,an isobutoxy group, a sec-butoxy group, a tert-butoxy group, an-pentyloxy group, a n-heptyloxy group, a n-octyloxy group, a n-nonyloxygroup, a n-decyloxy group, an undecyloxy group, a dodecyloxy group, atridecyloxy group, a tetradecyloxy group, a pentadecyloxy group, ahexadecyloxy group, a heptadecyloxy group, an octadecyloxy group, anonadecyloxy group, an eicosyloxy group, a cyclopropyloxy group, a2,2-dimethylcyclopropyloxy group, a cyclopentyloxy group, acyclohexyloxy group and a menthyloxy group.

The substituted alkoxy group includes, for example, alkoxy groupssubstituted with the aforementioned halogen atom, alkoxy, aryloxy,aralkyloxy, acyl, alkoxycarbonyl, aryloxycarbonyl, aralkyloxycarbonyl orcarboxyl. Specific examples thereof include a chloromethoxy group, afluoromethoxy group, a trifluoromethoxy group, a methoxymethoxy group,an ethoxymethoxy group and a methoxyethoxy group.

The substituted aryl group specifically includes a 2-methylphenyl group,a 4-chlorophenyl group, a 4-methylphenyl group, a 4-methoxyphenyl groupand a 3-phenoxyphenyl group.

The substituted or unsubstituted aryloxy group specifically includes aphenoxy group, a 2-methylphenoxy group, a 4-chlorophenoxy group, a4-methylphenoxy group, a 4-methoxyphenoxy group and a 3-phenoxyphenoxygroup.

The substituted or unsubstituted aralkyl group includes a benzyl groupand a phenylethyl group.

The substituted or unsubstituted aralkyloxy group includes a benzyloxygroup.

The substituted or unsubstituted acyl group includes a methylcarbonylgroup, an ethylcarbonyl group, a phenylcarbonyl group and abenzylcarbonyl group.

The substituted or unsubstituted alkoxycarbonyl group, the substitutedor unsubstituted aryloxycarbonyl group and the substituted orunsubstituted aralkyloxycarbonyl group include a methoxycarbonyl group,an ethoxycarbonyl group, a phenoxycarbonyl group and a benzyloxycarbonylgroup, respectively.

The arylhydrazine compound includes a compound of the formula (1)wherein Ar is benzothiazole, which is 2-hydrazinobenzothiazolerepresented by the following formula (1′):

wherein X represents the same group as the substituent of Ar.

The arylhydrazine compounds represented by Formulas (1) and (1′) includephenylhydrazine, 2-fluorophenylhydrazine, 3-fluorophenylhydrazine,4-fluorophenylhydrazine, 2-chlorophenylhydrazine,3-chlorophenylhydrazine, 4-chlorophenylhydrazine,2-bromophenylhydrazine, 3-bromophenylhydrazine, 4-bromophenylhydrazine,3-cyanophenylhydrazine, 4-cyanophenylhydrazine,2-methoxycarbonylphenylhydrazine, 2-n-butoxycarbonylphenylhydrazine,3-methoxycarbonylphenylhydrazine, 4-methoxycarbonylphenylhydrazine,2-nitrophenylhydrazine, 3-nitrophenylhydrazine, 4-nitrophenylhydrazine,2-methylphenylhydrazine, 3-methylphenylhydrazine,4-methylphenylhydrazine, 2-methoxyphenylhydrazine,3-methoxyphenylhydrazine, 4-methoxyphenylhydrazine,2-trifluoromethylphenylhydrazine, 3-trifluoromethylphenylhydrazine,4-trifluoromethylphenylhydrazine, 2-hydroxyphenylhydrazine,3-hydroxyphenylhydrazine, 4-hydroxyphenylhydrazine,2-carboxyphenylhydrazine, 3-carboxyphenylhydrazine,4-carboxyphenylhydrazine, 4-(chloromethyl)phenylhydrazine,2-sulfophenylhydrazine, 3-sulfophenylhydrazine, 4-sulfophenylhydrazine,4-sulfonamidophenylhydrazine, ethyl 4-sulfonate phenylhydrazine,3-methylsulfonphenylhydrazine, 2,3-dimethylphenylhydrazine,3,5-dimethylphenylhydrazine, 3,5-trifluoromethylphenylhydrazine,3,5-dinitrophenylhydrazine, 2,4-dinitrophenylhydrazine,2,4-dichlorophenylhydrazine, 2,6-diethylphenylhydrazine,2,5-difluorophenylhydrazine, 3,4-difluorophenylhydrazine,2,4-difluorophenylhydrazine, 3,5-difluorophenylhydrazine,3-chloro-4-fluorophenylhydrazine, 2-chloro-4-methylphenylhydrazine,2-carboxy-3-chlorophenylhydrazine,2-methoxycarbonyl-3-chlorophenylhydrazine,4-cyano-2-chlorophenylhydrazine,4-methyl-3-(chloromethyl)phenylhydrazine,4-methyl-3-(bromomethyl)phenylhydrazine,4-methyl-3-(methoxymethylcarbonyl)phenylhydrazine,4-methyl-3-(carbamoylmethyl)phenylhydrazine,4-methyl-3-cyanophenylhydrazine, 4-methyl-3-acetylphenylhydrazine,3-sulfonamido-2-acetylaminophenylhydrazine,2,3,5-trichlorophenylhydrazine, 3,4,5-trichlorophenylhydrazine,2,4-difluoro-5-nitrophenylhydrazine, 2,3,5,6-tetrafluorophenylhydrazine,2,3,4,5,6-pentafluorophenylhydrazine, 2-benzylphenylhydrazine,3-benzyloxyphenylhydrazine, 4-benzyloxyphenylhydrazine,2-aminophenylhydrazine, 3-aminophenylhydrazine, 4-aminophenylhydrazine,1-naphthylhydrazine, 2-naphthylhydrazine, 4-hydrazino-1,8-naphthalicacid anhydride, diethyl2-methyl-2-(3′-fluoro-4′-hydrazino)phenyl)malonate,4-chloro-3-hydroxy-2-fluorophenylhydrazine,4-trifluoromethyl-2,6-dichlorophenylhydrazine,5-methoxy-2,4-dichlorophenylhydrazine, 2-hydrazinopyridine,6-bromo-2-hydrazinopyridine, 2-hydrazinopyrimidine,4-trifluoromethyl-2-hydrazinopyrimidine,2-ethoxy-4-fluoro-6-hydrazinopyrimidine,2,4-dimethoxy-6-hydrazinopyrimidine, 2-hydrazinoquinoline,4-nitro-2-hydrazinoquinoline, 2-hydrazinobenzothiazole,2-hydrazinobenzoxazole, 2-hydrazino-4-methylbenzothiazole,2-hydrazino-5-methylbenzothiazole, 2-hydrazino-6-methylbenzoxazole,2-hydrazino-7-methylbenzothiazole, 2-hydrazino-4-ethylbenzothiazole,2-hydrazino-5-isopropylbenzoxazole, 2-hydrazino-4-methoxybenzothiazole,2-hydrazino-5-methoxybenzoxazole, 2-hydrazino-6-methoxybenzothiazole,2-hydrazino-7-methoxybenzothiazole,2-hydrazino-5,7-dimethoxybenzothiazole,2-hydrazino-4,6-dimethoxybenzothiazole,2-hydrazino-5,6-dimethoxybenzothiazole,2-hydrazino-4-ethoxybenzothiazole, 2-hydrazino-5-benzyloxybenzothiazole,2-hydrazino-7-benzyloxybenzothiazole, 2-hydrazino-4-chlorobenzothiazole,2-hydrazino-5-chlorobenzothiazole, 2-hydrazino-6-chlorobenzoxazole,2-hydrazino-4-fluorobenzothiazole, 2-hydrazino-5-fluorobenzoxazole,2-hydrazino-6-fluorobenzothiazole,2-hydrazino-5,7-dichlorobenzothiazole,2-hydrazino-4,6-dichlorobenzothiazole,2-hydrazino-5,6-dichlorobenzoxazole,2-hydrazino-5,7-difluorobenzothiazole,2-hydrazino-4,6-difluorobenzothiazole,2-hydrazino-5,6-difluorobenzoxazole,2-hydrazino-5-(2-methoxyethylcarbonyl)benzothiazole,2-hydrazino-6-bromobenzothiazole,2-hydrazino-5-trifluoromethylbenzothiazole,2-hydrazino-6-trifluoromethylbenzoxazole,2-hydrazino-5-cyanobenzothiazole, 2-hydrazino-6-cyanobenzoxazole,2-hydrazino-5-nitrobenzoxazole and 2-hydrazino-6-nitrobenzoth iazole.

Such arylhydrazine compounds may be addition salts with an acid such ashydrochloric acid, sulfuric acid or the like.

Hydrogen peroxide is usually used as a solution in water. Of course, asolution of hydrogen peroxide in an organic solvent may be used. Theconcentration of Hydrogen peroxide in the solution of hydrogen peroxidein water or an organic solvent is not particularly limited. However, inview of volume efficiency, safety and the like, it is practically 1 to60% by weight. As the solution of hydrogen peroxide in water, acommercially available hydrogen peroxide solution may be usually used asit is or after, if necessary, adjusting the concentration by dilution orconcentration. The solution of hydrogen peroxide in an organic solventmay be prepared, for example, by extracting the solution of hydrogenperoxide in water with an organic solvent or by distilling the solutionof hydrogen peroxide in water in the presence of an organic solvent.

The amount used of hydrogen peroxide is usually 1 mol or more per 1 molof the arylhydrazine compound and there is no upper limit in particular.However, in view of economy, the amount used of hydrogen peroxide ispractically 10 mol or less per 1 mol of the arylhydrazine compound.

The aryl compound is not particularly limited as long as it is acompound having an aromatic ring such as a benzene ring or a naphthalenering, or a heteroaromatic ring such as a pyridine ring, and having atleast one hydrogen atom on the aromatic ring or the heteroaromatic ring.The aromatic ring or the heteroaromatic ring may be substituted. Such asubstituent includes the aforementioned halogen atom, the aforementionedsubstituted or unsubstituted alkyl group, the aforementioned substitutedor unsubstituted alkoxy group, the aforementioned substituted orunsubstituted aryl group, the aforementioned substituted orunsubstituted aryloxy group, the aforementioned substituted orunsubstituted aralkyl group, the aforementioned substituted orunsubstituted aralkyloxy group, the substituted or unsubstituted acylgroup, the aforementioned substituted or unsubstituted carboalkoxygroup, the aforementioned substituted or unsubstituted carboaryloxygroup, the aforementioned substituted or unsubstituted carboaralkyloxy,a carboxyl group, a sulfo group, a cyano group, a hydroxyl group, anitro group and an amino group. Alternatively, adjacent substituents ofthese substituents may be taken together to form a ring structure.

Such aryl compound includes a compound represented by the formula (2):Ar′  (2)

wherein Ar′ is a substituted or unsubstituted aromatic group or asubstituted or unsubstituted heteroaromatic group, and has at least onehydrogen atom bound to the aforementioned group. The substituent is asdefined above.

Specific examples of the aryl compound include benzene, toluene, xylene,fluorobenzene, 1,2-difluorobenzene, 1,4-difluorobenzene, chlorobenzene,1,4-dichlorobenzene, 1,4-dibromobenzene, 1,3-dimethoxybenzene,1,4-dimethoxybenzene, 1,3,5-trichlorobenzene, bromobenzene,1,4-dibromobenzene, cyanobenzene, 1,4-dicyanobenzene,1-cyano-4-chlorobenzene, benzoic acid, methyl benzoate, terephthalicacid, dimethyl terephthalate, methyl 4-tert-butylbenzoate, aniline,nitrobenzene, 1,4-diaminobenzene, methoxybenzene, phenol, m-cresol,p-cresol, benzenesulfonic acid, p-toluenesulfonic acid, acetophenone,benzophenone, naphthalene, anthracene, pyrene, pyridine, quinoline andisoquinoline.

If the amount used of the aryl compound is not enough, self-couplingreaction of the arylhydrazine compound proceeds easily. Therefore, theamount used of the aryl compound is usually 10 mol or more per 1 mol ofthe arylhydrazine compound and there is no upper limit in particular.For example, if the aryl compound is in liquid form under reactioncondition, a greatly excessive amount of the aryl compound may be usedboth as a reaction material and a solvent.

The reaction between the aryihydrazine compound, hydrogen peroxide andthe aryl compound is usually performed in a solvent which is inert tothe reaction. Such a solvent includes ether solvents such as diethylether, methyl tert-butyl ether or tetrahydrofuran, ester solvents suchas ethyl acetate, nitrile solvents such as acetonitrile orpropionitrile, and aliphatic hydrocarbon solvents such as cyclohexane orn-heptane. The amount used of such a solvent is not particularlylimited, but in view of volume efficiency and the like, it ispractically 100 parts by weight or less per 1 part by weight of thearylhydrazine compound. Alternatively, as described above, if the arylcompound is in liquid form under reaction condition, it may be used as asolvent.

If the reaction temperature is too low, the reaction hardly proceedsand, if the reaction temperature is too high, side reaction such asdegradation of the starting material arylhydrazine compound or theproduced biaryl compound may proceed. Therefore, the practical reactiontemperature is in a range of 0° C. to 200° C.

The reaction between the arylhydrazine compound, hydrogen peroxide andthe aryl compound is usually performed by contacting or mixing the threecompounds. The order of mixing them is not particularly limited, but,preferably, the arylhydrazine compound is added to a mixture of hydrogenperoxide and the aryl compound.

The reaction may be performed under normal pressure, or may be performedunder increased pressure. In addition, progression of the reaction canbe confirmed by a conventional analysis means such as gaschromatography, high performance liquid chromatography, thin layerchromatography, NMR and IR.

In this reaction, since water is produced as a by-product as thereaction proceeds, it is preferable that the reaction is performed whileremoving water present in the reaction system or the reaction isperformed in the presence of a phase transfer catalyst. A method ofperforming the reaction while removing water present in a reactionsystem includes a method comprising coexistence of a dehydrating agentsuch as anhydrous magnesium sulfate, anhydrous sodium sulfate, anhydrouscalcium chloride or metaboric acid in a reaction system, for example, amethod using an azeotropic dehydrating apparatus.

The phase transfer catalyst is not particularly limited as long as ithas phase transfer ability, and examples thereof include a quaternaryammonium salt, an amine N-oxide compound, a quaternary phosphonium salt,a crown ether compound and a polyethylene glycol compound. Thequaternary ammonium salt or the amine N-oxide compound is preferable.

The quaternary ammonium salt includes quaternary ammonium chloridecompounds such as trioctylmethylammonium chloride, trioctylethylammoniumchloride, dilauryldimethylammonium chloride, lauryltrimethylammoniumchloride, stearyltrimethylammonium chloride,lauryldimethylbenzylammonium chloride, tricaprylmethylammonium chloride,tridecylmethylammonium chloride, trihexylmethylammonium chloride,tridecylmethylammonium chloride, tetrabutylammonium chloride,benzyltrimethylammonium chloride, benzyltriethylammonium chloride,N-laurylpyridinium chloride, N-cetylpyridinium chloride orN-laurylpicolinium chloride, quaternary ammonium bromide compounds inwhich the chlorine ion constituting the above quaternary ammoniumchloride compound is substituted with a bromine ion, quaternary ammoniumiodide compounds in which the chlorine ion constituting the abovequaternary ammonium chloride compound is substituted with an iodine ion,quaternary ammonium sulfite salts in which the chlorine ion constitutingthe above quaternary ammonium chloride compound is substituted with asulfite ion, quaternary ammonium sulfate salts in which the chlorine ionconstituting the above quaternary ammonium chloride compound issubstituted with a sulfate ion and quaternary ammonium hydrogen sulfatesalts in which the chlorine ion constituting the above quaternaryammonium chloride compound is substituted with a hydrogen sulfate ion.

The amine N-oxide compound includes trioctylamine N-oxide,dilaurylmethylamine N-oxide, lauryldimethylamine N-oxide,stearyldimethylamine N-oxide, tricaprylamine N-oxide, tridecylamineN-oxide, dimethyldodecylamine N-oxide, trihexylamine N-oxide,tridecylamine N-oxide, benzyldimethylamine N-oxide andbenzyldiethylamine N-oxide. These amine N-oxide compounds may beprepared by adding the corresponding amine compound to a reaction systemand then reacting the compound with hydrogen peroxide in the reactionsystem.

The quaternary phosphonium salt includes tetrabutylphosphonium bromide.The crown ether compound includes 12-crown-4,18-crown-6 andbenzo-18-crown-6. The polyethylene glycol compound includes polyethyleneglycol 600 (average molecular weight: 600), polyethylene glycol 700(average molecular weight: 700) and polyethylene glycol 800 (averagemolecular weight: 800).

The amount used of such a phase transfer catalyst may be a catalyticamount and it is usually 0.0005 mol or more per 1 mol of thearylhydrazine compound. There is no upper limit in particular, but inview of economy, the amount is 1 mol or less per 1 mol of thearylhydrazine compound.

After completion of the reaction, the reaction solution as it is or, ifnecessary, after remaining hydrogen peroxide is degraded with a reducingagent such as sodium thiosulfate may be subjected to concentration,crystallization or the like to isolate the desired biaryl compound.Alternatively, after water and/or a water-insoluble organic solvent isadded to the reaction solution if necessary, the reaction solution maybe extracted to obtain an organic layer and the organic layer may beconcentrated to isolate the biaryl compound. The isolated biarylcompound may be further purified by distillation or a conventionalpurification means such as column chromatography.

The water-insoluble organic solvent includes aromatic hydrocarbonsolvents such as toluene or xylene, halogenated hydrocarbon solventssuch as dichloromethane, chloroform or chlorobenzene, ether solventssuch as diethyl ether, methyl tert-butyl ether or tetrahydrofran andester solvents such as ethyl acetate, and the amount used is notparticularly limited.

The desired biaryl compound can be obtained by reaction between thearylhydrazine compound, hydrogen peroxide and the aryl compound. Thedesired biaryl compound can be produced in a further better yield byperforming such reaction in the presence of at least one speciesselected from the group consisting of the aforementioned groups (A) and(B).

The Group Va element metal or the compound thereof includes vanadiummetal, vanadium compounds such as vanadium oxide, ammonium vanadate or avanadium carbonyl complex, niobium metal, and niobium compounds such asniobium oxide, niobium chloride or a niobium carbonyl complex. The GroupVIa element metal or the compound thereof includes tungsten metal,tungsten compounds such as tungsten boride, tungsten carbide, tungstenoxide, ammonium tungstate or a tungsten carbonyl complex, molybdenummetal, and molybdenum compounds such as molybdenum boride, molybdenumoxide, molybdenum chloride or a molybdenum carbonyl complex.

The Group VIIa element metal or the compound thereof includes rheniummetal, rhenium compounds such as rhenium oxide, a complex of rheniumoxide, rhenium chloride, or alkylrhenium trioxide such as methylrheniumtrioxide. The Group VIIIa element metal or the compound thereof includescobalt metal, and cobalt compounds such as cobalt oxide, a complex ofcobalt oxide or cobalt chloride.

The Group Va element oxide obtained by reacting the Group Va elementmetal or a compound thereof with hydrogen peroxide includes vanadiumoxide obtained by reacting the aforementioned vanadium compound withhydrogen oxide, and niobium oxide obtained by reacting theaforementioned niobium compound with hydrogen peroxide. The Group VIaelement oxide obtained by reacting a Group VIa element metal or acompound thereof with hydrogen peroxide includes tungsten oxide obtainedby reacting the aforementioned tungsten metal or tungsten compound withhydrogen peroxide, and the molybdenum oxide obtained by reacting theaforementioned molybdenum metal or molybdenum compound with hydrogenperoxide.

The Group VIIa element oxide obtained by reacting the Group VIIa elementmetal or a compound thereof with hydrogen peroxide includes rheniumoxide obtained by reacting the aforementioned rhenium compound withhydrogen oxide. The Group VIIIa element oxide obtained by reacting theGroup VIIIa element metal or the compound thereof with hydrogen peroxideincludes cobalt oxide obtained by reacting the aforementioned cobaltcompound with hydrogen peroxide.

Among such metals and metal compounds, tungsten metal, tungstencompounds, cobalt compounds, niobium compounds, molybdenum metal,molybdenum compounds, rhenium compounds, tungsten oxide, cobalt oxide,niobium oxide, molybdenum oxide and a mixture thereof are preferable.Such metals and metal compounds may be used alone or as a mixturethereof.

Hydrogen peroxide which is used in producing the compounds of the group(B) (hereinafter, also referred to as metal oxide) is usually in a formof an aqueous solution. Of course, a solution of hydrogen peroxide in anorganic solvent may be used, but from a viewpoint of easy handling, itis preferable to use the solution of hydrogen peroxide in water. Thehydrogen peroxide concentration in the solution of hydrogen peroxide inwater or an organic solvent is not particularly limited, but in view ofvolume efficiency and safety, it is practically 1 to 60% by weight. Whenthe solution of hydrogen peroxide in water is used, a commerciallyavailable hydrogen peroxide solution may be used as it is or, ifnecessary, after adjusting the concentration by dilution orconcentration. When the solution of hydrogen peroxide in an organicsolvent is used, the solution prepared, for example, by extracting thesolution of hydrogen peroxide in water with an organic solvent or bydistilling the solution of hydrogen peroxide in water in the presence ofan organic solvent may be used.

The amount used of hydrogen peroxide in producing the compounds of thegroup (B) is usually 3 mol or more, preferably 5 mol or more per 1 molof the Group Va element metal or a compound thereof, the Group VIaelement metal or a compound thereof, the Group VIIa element metal or acompound thereof, or the Group VIIIa element metal or a compoundthereof. There is no upper limit in particular.

Preparation of the metal oxide is usually performed in an aqueoussolution. Of course, the preparation may be performed in an organicsolvent such as an ether solvent such as diethyl ether, methyltert-butyl ether or tetrahydrofran, an ester solvent such as ethylacetate or a nitrile solvent such as acetonitrile or propionitrile, or amixture of the organic solvent and water.

Preparation of the metal oxide is performed by mixing and contacting ametal or a metal compound of the group (A) with hydrogen peroxide and,in order to increase contact efficiency, such reaction is preferablyperformed with stirring so as to sufficiently disperse a metal or ametal compound of the group (A) in a solution for preparing metal oxide.In addition, in order to increase the contact efficiency between a metalor a metal compound of the group (A) and hydrogen peroxide and controlpreparation of the metal oxide more easily, for example, a metal or ametal compound of the group (A) in powder form is preferably used.

The temperature in preparation of metal oxide is usually −10 to 100° C.

A metal or a metal compound of the group (A) and hydrogen peroxide canbe reacted in water, an organic solvent or a mixture of an organicsolvent and water to dissolve all or a part of the metal or metalcompound of the group (A) and thereby prepare a homogeneous solution orsuspension containing metal oxide. The metal oxide may be isolated froma preparation solution, for example, by concentration and then may beused as a catalyst, or the preparation solution may be used as it is asthe catalyst. When the preparation solution is used as it is as thecatalyst, the amount used of hydrogen oxide in the reaction of thearylhydrazine compound, hydrogen peroxide and the aryl compound may bedetermined in view of the content of hydrogen peroxide in thepreparation solution.

Alternatively, preparation of the metal oxide and reaction between thearylhydrazine compound, hydrogen peroxide and the aryl compound may beperformed simultaneously by contacting and mixing each metal or themetal compound of the group (A), the arylhydrazine compound, hydrogenperoxide and the aryl compound.

The amount used of each metal or the metal compound of the group (A) isusually 0.001 mol or more per 1 mol of the arylhydrazine compound. Thereis no upper limit of the amount in particular, but in view of economy,it is practically 1 mol or less per 1 mol of the arylhydrazine compound.

In the reaction using the metal or a compound of the group (A), like thereaction without it, it is preferable that the reaction is performedwhile removing water present in the reaction system or the reaction isperformed in the presence of a phase transfer catalyst.

The phase transfer catalyst and the amount used thereof are as describedabove. Such a phase transfer catalyst may be also previously used inpreparation of the aforementioned metal oxide catalyst.

When the arylhydrazine compound, hydrogen peroxide and the aryl compoundare reacted in the presence of the metal compound and the desired biarylcompound is isolated by extraction or crystallization, the metalcompound catalyst is contained in an aqueous layer obtained byextraction of the reaction solution or in a filtrate obtained bycrystallization from the reaction solution. Thus, the aqueous layer orthe filtrate can be used in the present reaction again as it is or afterconcentration if necessary.

The biaryl compound thus obtained includes a biaryl compound representedby the formula (3):Ar—Ar′  (3)

wherein Ar and Ar′ are as defined above, and a 2-arylbenzothiazolecompound represented by the formula (3′):

wherein Ar′ is as defined above and X has the same meaning as that ofthe substituent of Ar, which is included in the biaryl compound of theformula (3).

Specific examples of the biaryl compound include biphenyl,2-fluorobiphenyl, 3-fluorobiphenyl, 4-fluorobiphenyl, 2-chlorobiphenyl,3-chlorobiphenyl, 4-chlorobiphenyl, 2-bromobiphenyl, 3-bromobiphenyl,4-bromobiphenyl, 2-phenyltoluene, 3-phenyltoluene, 4-biphenyltoluene,2-methoxybiphenyl, 3-cyanobiphenyl, 4-carbomethoxybiphenyl,2-carbomethoxybiphenyl, 2-phenylbenzoic acid,2-n-butoxycarbonylbiphenyl, 4-nitrobiphenyl, 2-trifluoromethylbiphenyl,3-trifluoromethylbiphenyl, 4-trifluoromethylbiphenylhydrazine,2-sulfobiphenyl, 4-sulfonamidobiphenyl, ethyl 4-sulfonate biphenyl,3-methylsulfonbiphenyl, 2,4-dinitrobiphenyl, 2,4-dichlorobiphenyl,2,4-difluorobiphenyl, 3,5-difluorobiphenyl,3,5-di(trifluoromethyl)biphenyl, 3-chloro-4-fluorobiphenyl,2-carboxy-3-chlorobiphenyl, 2-methoxycarbonyl-3-chlorobiphenyl,3-sulfonamido-2-acetylaminobiphenyl, 2,3,5-trichlorobiphenyl,2,4-difluoro-5-nitrobiphenyl, 2,3,5,6-tetrafluorobiphenyl,2,3,4,5,6-pentafluorobiphenyl, 2-benzylbiphenyl, 3-benzyloxybiphenyl,4-benzyloxybiphenyl, 4-phenyl-1,8-naphthalic acid anhydride, diethyl2-methyl-2-((3′-fluoro-4′-phenyl)phenyl)malonate,4-chloro-3-hydroxy-2-fluorobiphenyl,4-trifluoromethyl-2,6-dichlorobiphenyl, 5-methoxy-2,4-dichlorobiphenyl,6-bromo-2-phenylpyridine, 2-phenylpyrimidine,4-trifluoromethyl-2-phenylpyrimidine,2-ethoxy-4-fluoro-6-phenylpyrimidine, 2,4-dimethoxy-6-phenylpyrimidine,2-phenylquinoline, 4-nitro-2-phenylquinoline,3-tert-butyl-2-cyanobiphenyl,4-(2′,5′-dicarbomethoxyphenyl)-trifluoromethylbenzene, 3-phenylphenol,2-aminobiphenyl, 4-biphenylacetic acid,4-methyl-2-(methoxymethylcarbonyl)biphenyl,4-methyl-3-(methoxymethylcarbonyl)biphenyl,4-methyl-3-(chloromethyl)biphenyl, 4-methyl-3-cyanobiphenyl,4-methyl-2′,6′-dimethoxybiphenyl, 2,2′-difluorobiphenyl,3,3′-dichlorobiphenyl, 4,4′-dibromobiphenyl, 3,5-dinitrobiphenyl,3,5-dinitrophenyltoluene, 2,4′-chlorofluorobiphenyl, 2-phenylpyridine,3-phenylpyridine, 4-phenylpyridine, 2,2′-bipyridyl, 3,3′-bipyridyl,4,4′-bipyridyl, 1-phenylnaphthalene, 1,1′-binaphthyl,2-phenylbenzothiazole, 2-phenylbenzoxazole,2-(2-methylphenyl)benzothiazole, 2-(3-methylphenyl)benzothiazole,2-(4-methylphenyl)benzothiazole,2-(3-methyl-4-methoxyphenyl)benzothiazole,2-(2-chlorophenyl)benzothiazole, 2-(2-fluorophenyl)benzothiazole,2-(2,4-dichlorophenyl)benzothiazole, 2-(2,5-dichlorophenyl)benzoxazole,2-(2,5-dimethylphenyl)benzothiazole, 2-(2,5-difluorophenyl)benzoxazole,2-(4-nitrophenyl)benzothiazole, 2-(2-pyridyl)benzothiazole,2-phenyl-4-methylbenzothiazole, 2-phenyl-5-methylbenzoxazole,2-phenyl-6-methylbenzothiazole, 2-phenyl-7-methylbenzothiazole,2-phenyl-4-ethylbenzoxazole, 2-phenyl-5-isopropylbenzothiazole,2-phenyl-4-methoxybenzothiazole,2-(4-methoxyphenyl)-5-methoxybenzothiazole,2-phenyl-6-methoxybenzothiazole, 2-phenyl-7-methoxybenzoxazole,2-(4-methoxyphenyl)-5,7-dimethoxybenzothiazole,2-phenyl-4,6-dimethoxybenzothiazole, 2-phenyl-5,6-dimethoxybenzoxazole,2-phenyl-4-ethoxybenzothiazole, 2-phenyl-5-benzyloxybenzothiazole,2-phenyl-7-benzyloxybenzothiazole, 2-phenyl-4-chlorobenzothiazole,2-phenyl-5-chlorobenzoxazole, 2-phenyl-6-chlorobenzothiazole,2-phenyl-4-fluorobenzothiazole, 2-phenyl-5-fluorobenzoxazole,2-phenyl-6-fluorobenzothiazole,2-(3-methylphenyl)-6-fluorobenzothiazole,2-(3-methyl-4-nitrophenyl)-6-fluorobenzothiazole,2-phenyl-5,7-dichlorobenzothiazole, 2-phenyl-4,6-dichlorobenzoxazole,2-phenyl-5,6-dichlorobenzothiazole, 2-phenyl-5,7-difluorobenzoxazole,2-phenyl-4,6-difluorobenzothiazole, 2-phenyl-5,6-difluorobenzothiazole,2-phenyl-5-(2-carbomethoxyethyl)benzothiazole,2-phenyl-6-bromobenzoxazole, 2-phenyl-5-trifluoromethylbenzothiazole,2-phenyl-6-trifluoromethylbenzoxazole, 2-phenyl-5-cyanobenzothiazole,2-phenyl-6-cyanobenzoxazole, 2-phenyl-5-nitrobenzothiazole and2-phenyl-6-nitrobenzothiazole.

Then, the process for producing a biaryl compound which comprisesreacting the arylhydrazine compound and hydrogen peroxide in thepresence of at least one species selected from the group consisting ofgroups (A) and (B) will be explained.

By reacting the arylhydrazine compound and hydrogen peroxide, a biarylcompound in which two molecules of an arylhydrazine compound areself-coupled is obtained. For example, when phenylhydrazine is used asthe arylhydrazine compound, biphenyl is obtained.

The arylhydrazine compound includes the same compounds as thosedescribed above, for example, the arylhydrazine compound of the formula(1). Hydrogen peroxide includes the same hydrogen peroxides as thosedescribed above.

The amount used of hydrogen peroxide is usually 1 mol or more per 1 molof the arylhydrazine compound and there is no upper limit in particular.

The reaction between the arylhydrazine compound and hydrogen peroxide isusually performed in a solvent which is inert to the reaction. Suchsolvent includes ether solvents such as diethyl ether, methyl tert-butylether or tetrahydrofuran, ester solvents such as ethyl acetate, nitrilesolvents such as acetonitrile or propionitrile, and aliphatichydrocarbon solvents such as cyclohexane or n-heptane. The amount usedof such solvent is not particularly limited, but in view of volumeefficiency, it is practically 100 parts by weight or less per 1 part byweight of the arylhydrazine compound.

If the reaction temperature is too low, the reaction hardly proceedsand, if the reaction temperature is too high, side reaction such asdegradation of the starting material arylhydrazine compound and theproduced biaryl compound may proceed. Therefore, the practical reactiontemperature is in a range of 0° C. to 200° C.

The reaction is usually performed by contacting and mixing thearylhydrazine compound with hydrogen peroxide, and the order of mixingthem is not limited.

The reaction between the arylhydrazine compound and hydrogen peroxidemay be performed under normal pressure or under pressurized pressure. Inaddition, progression of the reaction can be confirmed by a conventionalanalysis means such as gas chromatography, high performance liquidchromatography, thin layer chromatography, NMR and IR.

Since water is produced as a by-product in this reaction as the reactionproceeds, like the aforementioned reaction between the arylhydrazinecompound, hydrogen peroxide and the aryl compound, it is preferable toperform the reaction while removing water present in the reaction systemor perform the reaction in the presence of a phase transfer catalyst.Examples of a method of performing the reaction while removing waterpresent in the reaction system are the same as the described above.Examples of the phase transfer catalyst are also the same as describedabove.

After completion of the reaction, the reaction solution as it is or, ifnecessary, after remaining hydrogen peroxide is degraded with a reducingagent such as sodium thiosulfate may be subjected to concentration,crystallization or the like to isolate the desired biaryl compound.Alternatively, after water and/or a water-insoluble organic solvent isadded to the reaction solution if necessary, the reaction solution maybe extracted to obtain an organic layer and the organic layer may beconcentrated to isolate a biaryl compound. The isolated biaryl compoundmay be further purified by distillation or a conventional purificationmeans such as column chromatography.

Examples of the water-insoluble organic solvent are the same asdescribed above, and its amount used is not particularly limited.

The desired biaryl compound can be obtained by reacting thearylhydrazine compound with hydrogen peroxide and the biaryl compoundcan be produced in a further better yield by performing such reaction inthe presence of at least one catalyst selected from the group consistingof the groups (A) and (B) (hereinafter, abbreviated as the metalcompound).

Examples of the metal compound are the same as described above. Itsamount used may be a catalytic amount, and it is usually 0.001 mol ormore per 1 mol of the arylhydrazine compound. There is no upper limit ofthe amount in particular, but in view of economy, it is practically 1mol or less per 1 mol of the arylhydrazine compound.

In the reaction using the metal compound, like the reaction without it,it is preferable that the reaction is performed while removing waterpresent in the reaction system or the reaction is performed in thepresence of a phase transfer catalyst.

Examples of the phase transfer catalyst are the same as described above.Its use amount is also as described above. Such a phase transfercatalyst may be previously used in preparation of the aforementionedmetal oxide catalyst.

When the arylhydrazine compound and hydrogen peroxide are reacted in thepresence of the metal compound and the desired biaryl compound isisolated by extraction or crystallization, the metal compound catalystis contained in an aqueous layer obtained by extraction of the reactionsolution or in a filtrate obtained by crystallization from the reactionsolution. Thus, the aqueous layer or the filtrate can be used in thepresent reaction again as it is or after concentration if necessary.

The biaryl compound thus obtained includes a biaryl compound representedby the formula (4):Ar—Ar   (4)

wherein Ar is as defined above, and specific examples thereof includebiphenyl, 2,2′-difluorobiphenyl, 3,3′-dichlorobiphenyl,4,4′-dibromobiphenyl, 2,2′-bipyridyl, 3,3′-bipyridyl, 4,4′-bipyridyl and1,1′-binaphthyl.

EXAMPLES

The following Examples further illustrate the present invention indetail, but the present invention is not limited by these Examples.

Example 1

Into a 50 mL flask, toluene (15 g) and anhydrous magnesium sulfate (3 g)were charged and 30% by weight hydrogen peroxide solution in water (1100mg) was added dropwise over 5 minutes thereto. Then, the innertemperature of the mixture was increased to 80° C. A mixture ofphenylhydrazine (220 mg) and toluene (15 g) was added dropwise at thesame temperature over 1 hour into the flask and the mixture was stirredand retained for another 1 hour to be reacted. After cooled to roomtemperature, water (10 g) was added, and the mixture was stirred andthen allowed to stand at room temperature to separate layers. Theobtained organic layer containing phenyltoluene was analyzed by gaschromatography. As a result, the yield of phenyltoluene was found to be27% and the isomer ratio was found to be o-isomer: m-isomer:p-isomer=61:23:16.

Example 2

Into a 50 mL flask, toluene (15 g), 30% by weight hydrogen peroxidesolution in water (1350 mg) and trimethyloctylammonium hydrogen sulfatesalt (60 mg) were charged and the inner temperature of the mixture wasincreased to 80° C. A mixture of phenylhydrazine (220 mg) and toluene (5g) was added dropwise at the same temperature over 3 hours into theflask and the mixture was stirred and retained for another 1 hour to bereacted. After cooled to room temperature, water (10 g) was added, andthe mixture was stirred and then allowed to stand at room temperature toseparate layers. The obtained organic layer containing phenyltoluene wasanalyzed by gas chromatography. As a result, the yield of phenyltoluenewas found to be 27% and the isomer ratio was found to be o-isomer:m-isomer: p-isomer=63:22:15.

Example 3

Into a 50 mL flask, toluene (15 g) and 30% by weight hydrogen peroxidesolution in water (1350 mg) were charged and the inner temperature ofthe mixture was increased to 80° C. A mixture of phenylhydrazine (220mg) and toluene (5 g) was added dropwise at the same temperature over 3hours into the flask and the mixture was stirred and retained foranother 1 hour to be reacted. After cooled to room temperature, water(10 g) was added, and the mixture was stirred and then allowed to standat room temperature to separate layers. The obtained organic layercontaining phenyltoluene was analyzed by gas chromatography. As aresult, the yield of phenyltoluene was found to be 16.3% and the isomerratio was found to be o-isomer: m-isomer: p-isomer=60:22:18.

Example 4

Into a 100 mL flask, tungsten metal (40 mg) and 30% by weight hydrogenperoxide solution in water (250 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was adjusted to 30° C. and benzene (15 g) and anhydrousmagnesium sulfate (3 g) were added thereto. Then, 30% by weight hydrogenperoxide solution in water (1100 mg) was added dropwise over 5 minutes.After the inner temperature of the mixture was increased to 80° C., amixture of 4-methylphenylhydrazine (250 mg) and benzene (15 g) was addeddropwise over 1 hour and the mixture was then stirred and retained atthe same temperature for another 1 hour to be reacted. After cooled toroom temperature, water (10 g) was added, and the mixture was stirredand then allowed to stand to separate layers. The obtained organic layercontaining 4-phenyltoluene was analyzed by gas chromatography. As aresult, the yield of 4-phenyltoluene was found to be 40%.

Example 5

Into a 100 mL flask, tungsten metal (40 mg) and 30% by weight hydrogenperoxide solution in water (250 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was adjusted to 30° C. and benzene (15 g) andtrimethyloctylammonium hydrogen sulfate salt (60 mg) were added thereto.Then, 30% by weight hydrogen peroxide solution in water (1100 mg) wasadded dropwise over 5 minutes. After the inner temperature of themixture was increased to 80° C., a mixture of 4-chlorophenylhydrazine(285 mg) and benzene (15 g) was added dropwise over 1 hour and themixture was then stirred and retained at the same temperature foranother 1 hour to be reacted. After cooled to room temperature, water(10 g) was added, and the mixture was stirred and then allowed to standto separate layers. The obtained organic layer containing4-chlorobiphenyl was analyzed by gas chromatography. As a result, theyield of 4-chlorobiphenyl was found to be 82%.

Example 6

In the same manner as that of Example 5 except that2-fluorophenylhydrazine (252 mg) was used in place of4-chlorophenylhydrazine (285 mg), an organic layer containing2-fluorobiphenyl was obtained. The organic layer was analyzed by gaschromatography and as a result, the yield of 2-fluorobiphenyl was foundto be 80%.

Example 7

Into a 100 mL flask, tungsten metal (40 mg) and 30% by weight hydrogenperoxide solution in water (250 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was adjusted to 30° C. and benzene (15 g) andtrimethyloctylammonium hydrogen sulfate salt (60 mg) were added thereto.Then, 30% by weight hydrogen peroxide solution in water (1100 mg) wasadded dropwise over 5 minutes. After the inner temperature of themixture was increased to 80° C., a mixture of 4-nitrophenylhydrazine(306 mg) and ethyl acetate (10 g) was added dropwise over 1 hour and themixture was then stirred and retained at the same temperature foranother 1 hour to be reacted. After cooled to room temperature, water(10 g) was added, and the mixture was stirred and then allowed to standto separate layers. The obtained organic layer containing4-nitrobiphenyl was analyzed by gas chromatography. As a result, theyield of 4-nitrobiphenyl was found to be 67%.

Example 8

Into a 100 mL flask, tungsten metal (200 mg) and 30% by weight hydrogenperoxide solution in water (1.0 g) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was adjusted to 30° C. and benzene (40 g) andtrimethyloctylammonium hydrogen sulfate salt (300 mg) were addedthereto. Then, 30% by weight hydrogen peroxide solution in water (11.0g) was added dropwise over 5 minutes. After the inner temperature of themixture was increased to 80° C., a mixture of2,4-difluorophenylhydrazine (2.88 g) and benzene (10 g) was addeddropwise over 3 hours and the mixture was then stirred and retained atthe same temperature for another 1 hour to be reacted. After cooled toroom temperature, water (20 g) was added, and the mixture was stirredand then allowed to stand to separate layers. The obtained organic layercontaining 2,4-difluorobiphenyl was analyzed by gas chromatography. As aresult, the yield of 2,4-difluorobiphenyl was found to be 90%. From thissolution, the solvent was distilled off to obtain a yellow crystal (3.5g). The purity of the crystal was found to be 97.5% (GC areapercentage).

Example 9

Into a 200 mL flask, tungsten metal (400 mg) and water (2 g) was addedand warmed to 40° C. with stirring. Then, 30% by weight hydrogenperoxide solution in water (2.5 g) was added dropwise over 30 minutesand the mixture was stirred and retained at the same temperature for 0.5hours to prepare an aqueous solution of tungsten metal oxide. The innertemperature of the aqueous solution was adjusted to 30° C. and benzene(90 g) and trimethyloctylammonium hydrogen sulfate salt (600 mg) wereadded thereto. Then, 30% by weight hydrogen peroxide solution in water(33.0 g) was added dropwise over 5 minutes. After the inner temperatureof the mixture was increased to 80° C., a mixture of4-fluorophenylhydrazine (7.56 g) and benzene (20 g) was added dropwiseover 5 hours and the mixture was then stirred and retained at the sametemperature for another 1 hour to be reacted. After cooled to roomtemperature, water (20 g×2) was added and the mixture was stirred andthen allowed to stand to separate layers. The obtained organic layercontaining 4-fluorobiphenyl was analyzed by gas chromatography. As aresult, the yield of 4-fluorobiphenyl was found to be 90%. From thissolution, the solvent was distilled off to obtain a yellow crystal (7.5g). The purity of the crystal was found to be 97.0% (GC areapercentage).

Example 10

Into a 100 mL flask, tungsten metal (200 mg) and 30% by weight hydrogenperoxide solution in water (1.0 g) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was adjusted to 30° C. and benzene (40 g) andtrimethyloctylammonium hydrogen sulfate salt (300 mg) were addedthereto. Then, 30% by weight hydrogen peroxide solution in water (11.0g) was added dropwise over 5 minutes. After the inner temperature of themixture was increased to 80° C., a mixture of diethyl2-methyl-2-((3′-fluoro-4′-hydrazino)phenyl)malonate (1.0 g) and benzene(10 g) was added dropwise over 3 hours and the mixture was then stirredand retained at the same temperature for another 1 hour to be reacted.After cooled to room temperature, water (20 g) was added, and themixture was stirred and then allowed to stand to separate layers. Theobtained organic layer containing diethyl2-methyl-2-((3′-fluoro-4′-phenyl)phenyl)malonate was analyzed by gaschromatography. As a result, the yield of diethyl2-methyl-2-((3′-fluoro-4′-phenyl)phenyl)malonate was found to be 80%.

Example 11

In the same manner as that of Example 5 except that3-cyanophenylhydrazine (266 mg) was used in place of4-chlorophenylhydrazine (285 mg), an organic layer containing3-cyanobiphenyl was obtained. The organic layer was analyzed by gaschromatography and as a result, the yield of 3-cyanobiphenyl was foundto be 85%.

Example 12

In the same manner as that of Example 5 except that4-trifluoromethylphenylhydrazine (353 mg) was used in place of4-chlorophenylhydrazine (285 mg), an organic layer containing4-trifluoromethylbiphenyl was obtained. The organic layer was analyzedby gas chromatography and as a result, the yield of4-trifluoromethylbiphenyl was found to be 88%.

Example 13

In the same manner as that of Example 7 except that2-carbobutoxyphenylhydrazine (306 mg) was used in place of4-nitrophenylhydrazine (306 mg), an organic layer containing2-carbobutoxybiphenyl was obtained. The organic layer was analyzed bygas chromatography and as a result, the yield of 2-carbobutoxybiphenylwas found to be 30%.

Example 14

In the same manner as that of Example 7 except that2-hydrazino-6-bromopyridine (120 mg) was used in place of4-nitrophenylhydrazine (306 mg), an organic layer containing2-phenyl-6-bromopyridine was obtained. The organic layer was analyzed bygas chromatography and as a result, the yield of2-phenyl-6-bromopyridine was found to be 42%.

Example 15

In the same manner as that of Example 7 except that2-hydrazino-4-trifluoromethylpiperazine (360 mg) was used in place of4-nitrophenylhydrazine (306 mg), an organic layer containing2-phenyl-4-trifluoromethylpiperazine was obtained. The organic layer wasanalyzed by gas chromatography and as a result, the yield of2-phenyl-4-trifluoromethylpiperazine was found to be 26%.

Example 16

Into a 100 mL flask, tungsten metal (40 mg) and 30% by weight hydrogenperoxide solution in water (250 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was adjusted to 30° C. and 4-tert-butylcyanobenzene (10g) and trimethyloctylammonium hydrogen sulfate salt (60 mg) were addedthereto. Then, 30% by weight hydrogen peroxide solution in water (1100mg) was added dropwise over 5 minutes. After the inner temperature ofthe mixture was increased to 80° C., a mixture of phenylhydrazine (216mg) and ethyl acetate (5 g) was added dropwise over 2 hours and themixture was then stirred and retained at the same temperature foranother 1 hour to be reacted. After cooled to room temperature, water(10 g) was added, and the mixture was stirred and then allowed to standto separate layers. The obtained organic layer containing3-tert-butyl-2-cyanobiphenyl was analyzed by gas chromatography. As aresult, the yield of 3-tert-butyl-2-cyanobiphenyl was found to be 25%.

Example 17

Into a 100 mL flask, tungsten metal (60 mg) and 30% by weight hydrogenperoxide solution in water (400 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was adjusted to 30° C. and dimethyl terephthalate (15g), ethyl acetate (15 g) and trimethyloctylammonium hydrogen sulfatesalt (60 mg) were added thereto. Then, 30% by weight hydrogen peroxidesolution in water (3.3 g) was added dropwise over 5 minutes. After theinner temperature of the mixture was increased to 80° C., a mixture of4-trifluoromethylphenylhydrazine (1.0 g). and ethyl acetate (15 g) wasadded dropwise over 2 hours and the mixture was then stirred andretained at the same temperature for another 1 hour to be reacted. Aftercooled to room temperature, water (10 g) was added, and the mixture wasstirred and then allowed to stand to separate layers. The obtainedorganic layer containing4-(2′,5′-dicarbomethoxyphenyl)-trifluoromethylbenzene was analyzed bygas chromatography. As a result, the yield of4-(2′,5′-dicarbomethoxyphenyl)-trifluoromethylbenzene was found to be30%.

Example 18

Into a 50 mL flask, tungsten metal (40 mg) and 30% by weight hydrogenperoxide solution in water (250 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was cooled to 30° C. and toluene (15 g), 30% by weighthydrogen peroxide solution in water (1100 mg) and trimethyloctylammoniumhydrogen sulfate salt (60 mg) were added thereto. After the innertemperature of the mixture was increased to 50° C., a mixture ofphenylhydrazine (220 mg) and toluene (5 g) was added dropwise at thesame temperature over 1 hour and the mixture was then stirred andretained for another 1 hour to be reacted. After cooled to roomtemperature, water (10 g) was added, and the mixture was stirred andthen allowed to stand at room temperature to separate layers. Theobtained organic layer containing phenyltoluene was analyzed by gaschromatography. As a result, the yield of phenyltoluene was found to be39% and the isomer ratio was found to be o-isomer: m-isomer:p-isomer=65.4:20.4:14.2.

Example 19

Into a 50 mL flask, tungsten metal (40 mg) and 30% by weight hydrogenperoxide solution in water (250 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was cooled to 30° C. and toluene (15 g), 30% by weighthydrogen peroxide solution in water (1100 mg) and dimethyldodecylamineN-oxide (60 mg) were added thereto. After the inner temperature of themixture was increased to 60° C., a mixture of phenylhydrazine (220 mg)and toluene (5 g) was added dropwise at the same temperature over 3hours and the mixture was then stirred and retained for another 1 hourto be reacted. After cooled to room temperature, water (10 g) was added,and the mixture was stirred and then allowed to stand at roomtemperature to separate layers. The obtained organic layer containingphenyltoluene was analyzed by gas chromatography. As a result, the yieldof phenyltoluene was found to be 35% and the isomer ratio was found tobe o-isomer: m-isomer: p-isomer=62:24:14.

Example 20

Into a 50 mL flask, tungsten metal (40 mg) and 30% by weight hydrogenperoxide solution in water (250 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was cooled to 30° C. and toluene (15 g) and anhydrousmagnesium sulfate (3 g) were added. After 30% by weight hydrogenperoxide solution in water (1100 mg) was added dropwise over 5 minutes,the inner temperature of the mixture was increased to 80° C. A mixtureof phenylhydrazine (220 mg) and toluene (15 g) was added dropwise at thesame temperature over 1 hour and the mixture was then stirred andretained for another 1 hour to be reacted. After cooled to roomtemperature, water (10 g) was added, and the mixture was stirred andthen allowed to stand at room temperature to separate layers. Theobtained organic layer containing phenyltoluene was analyzed by gaschromatography. As a result, the yield of phenyltoluene was found to be40% and the isomer ratio was found to be o-isomer: m-isomer:p-isomer=64:21:15.

Example 21

In the same manner as that of Example 20 except that cobalt oxide (12mg) was used in place of tungsten metal (40 mg), an organic layercontaining phenyltoluene was obtained. The yield of phenyltoluene wasfound to be 31%, and the isomer ratio was found to be o-isomer:m-isomer: p-isomer=64:21:15.

Example 22

In the same manner as that of Example 20 except that niobium metal (20mg) was used in place of tungsten metal (40 mg), an organic layercontaining phenyltoluene was obtained. The yield of phenyltoluene wasfound to be 32% and the isomer ratio was found to be o-isomer: m-isomer:p-isomer=64:21:15.

Example 23

In the same manner as that of Example 18 except that molybdenum metal(20 mg) was used in place of tungsten metal, phenyltoluene was obtained.The yield of phenyltoluene was found to be 30% and the isomer ratio wasfound to be o-isomer: m-isomer: p-isomer=63:23:14.

Example 24

In the same manner as that of Example 20 except that methylrheniumtrioxide is used in place of tungsten metal, phenyltoluene is obtained.

Example 25

Into a 50 mL flask, tungsten metal (40 mg) and 30% by weight hydrogenperoxide solution in water (250 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was cooled to 30° C. and chlorobenzene (15 g) andanhydrous magnesium sulfate (3 g) were added. After 60% by weighthydrogen peroxide solution in water (900 mg) was added dropwise over 5minutes, the inner temperature of the mixture was increased to 80° C. Amixture of phenylhydrazine (220 mg) and chlorobenzene (15 g) was addeddropwise at the same temperature over 1 hour and the mixture was thenstirred and retained for another 1 hour to be reacted. After cooled toroom temperature, water (10 g) was added, and the mixture was stirredand then allowed to stand at room temperature to separate layers. Theobtained organic layer containing chlorobiphenyl was analyzed by gaschromatography. As a result, the yield of chlorobiphenyl was found to be39% and the isomer ratio was found to be o-isomer: m-isomer:p-isomer=62:20:18.

Example 26

Into a 50 mL flask, tungsten metal (40 mg) and 30% by weight hydrogenperoxide solution in water (250 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was cooled to 30° C. and pyridine (10 g) and anhydrousmagnesium sulfate (3 g) were added. After 60% by weight hydrogenperoxide solution in water (900 mg) was added dropwise over 5 minutes,the inner temperature of the mixture was increased to 80° C. A mixtureof phenylhydrazine (220 mg) and pyridine (8 g) was added dropwise at thesame temperature over 1 hour and the mixture was then stirred andretained for another 1 hour to be reacted. After cooled to roomtemperature, water (10 g) was added, and the mixture was stirred andthen allowed to stand at room temperature to separate layers. Theobtained organic layer containing phenylpyridine was analyzed by gaschromatography. As a result, the yield of phenylpyridine was found to be27% and the isomer ratio was found to be o-isomer: m-isomer:p-isomer=47:28:25.

Example 27

Into a 50 mL flask, tungsten metal (40 mg) and 30% by weight hydrogenperoxide solution in water (250 mg) were charged and the innertemperature of the mixture was increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was cooled to 30° C. and toluene (15 g), 30% by weighthydrogen peroxide solution in water (1100 mg) and trimethyloctylammoniumhydrogen sulfate salt (60 mg) were added. After the inner temperature ofthe mixture was increased to 80° C., a mixture of3,5-dinitrophenylhydrazine (400 mg) and toluene (5 g) was added dropwiseat the same temperature over 1 hour and the mixture was then stirred andretained for another 1 hour to be reacted. After cooled to roomtemperature, water (10 g) was added, and the mixture was stirred andthen allowed to stand at room temperature to separate layers. Theobtained organic layer containing 3,5-dinitrophenyltoluene was analyzedby gas chromatography. As a result, the yield of3,5-dinitrophenyltoluene (a mixture of three isomers) was found to be70%.

Example 28

Into a 50 mL flask, acetonitrile (10 g) and anhydrous magnesium sulfate(3 g) were charged and 30% by weight hydrogen peroxide solution in water(1100 mg) was added dropwise over 5 minutes. The inner temperature ofthe mixture was then increased to 80° C. and phenylhydrazine (220 mg)was added dropwise over 5 minutes. The mixture was then stirred andretained at the same temperature for another 1 hour to be reacted. Aftercooled to room temperature, water (10 g) was added, and the mixture wasstirred and then allowed to stand to separate layers. The obtainedorganic layer containing biphenyl was analyzed by gas chromatography. Asa result, the yield of biphenyl was found to be 6%.

Example 29

Into a 50 mL flask, tungsten metal (40 mg) and 30% by weight aqueoushydrogen peroxide solution in water (250 mg) were charged and the innertemperature of the mixture was then increased to 40° C. The mixture wasstirred and retained at the same temperature for 0.5 hours to prepare anaqueous solution of tungsten metal oxide. The inner temperature of theaqueous solution was cooled to 30° C. and benzene (15 g), 30% by weightaqueous hydrogen peroxide solution in water (1100 mg) andtrimethyloctylammonium hydrogen sulfate salt (60 mg) were added. Afterthe inner temperature of the mixture was increased to 60° C., a mixtureof 2-hydrazinobenzothiazole (330 mg) and benzene (5 g) was addeddropwise at the same temperature over 1 hour and the mixture was thenstirred and retained at the same temperature for another 1 hour to bereacted. After cooled to room temperature, water (10 g) was added, andthe mixture was stirred and then allowed to stand to separate layers. Anorganic layer containing 2-phenylbenzothiazole was obtained and theyield of 2-phenylbenzothiazole was found to be 40%.

Example 30

Into a 50 mL flask, benzene (15 g) and 13% by weight aqueous hydrogenperoxide solution in water (5.8 g) were charged and the innertemperature of the mixture was then increased to 60° C. A mixture of2-hydrazinobenzothiazole (330 mg) and benzene (5 g) was added dropwiseat the same temperature over 1 hour and the mixture was then stirred andretained at the same temperature for another 1 hour to be reacted. Aftercooled to room temperature, water (10 g) was added, and the mixture wasstirred and then allowed to stand to separate layers. An organic layercontaining 2-phenylbenzothiazole was obtained and the yield of2-phenylbenzothiazole was found to be 10%.

Example 31

In the same manner as that of Example 29 except that2-hydrazinobenzoxazole (306 mg) was used in place of2-hydrazinobenzothiazole (330 mg), an organic layer containing2-phenylbenzoxazole was obtained. The yield of 2-phenylbenzoxazole wasfound to be 23%.

Industrial Applicability

According to the process of the present invention, a biaryl compound canbe easily obtained from an arylhydrazine compound, or an arylhydrazinecompound and an aryl compound by using hydrogen peroxide, which isinexpensive, easy to use and converted into harmless water afterreaction, that is, clean and excellent. Moreover, a biaryl compound canbe obtained in a further better yield by performing the reaction in thepresence of a Group Va element metal or a compound thereof, a Group VIaelement metal or a compound thereof, a Group VIIa element metal or acompound thereof, a Group VIIIa element metal or a compound thereof orthe like, such as easily available tungsten metal or molybdenum metal,which is industrially advantageous.

1. A process for producing a biaryl compound, which comprises reactingan arylhydrazine compound, hydrogen peroxide and an aryl compound at areaction temperature of 0 to 200° C.; wherein the arylhydrazine compoundis represented by the formula (1):Ar—NHNH₂   (1) wherein Ar represents a substituted or unsubstitutedpyridinyl group, wherein substituents of the pyridinyl group are analkyl group, an alkoxy group, an alkoxycarbonyl group, an aryl group, anaryloxy group, an aryloxycarbonyl group, an aralkyl group, an aralkyloxygroup, an aralkyloxycarbonyl group, an acyl group, a halogen atom, acarboxyl group, a sulfo group (—SO₃H), a sulfonamido group, a sulfonicacid (aryl or alkyl) ester group, a sulfonyl group, a cyano group, ahydroxyl group, a nitro group, an amino group, or an amido group, thearyl compound is represented by the formula (2):Ar′  (2) wherein Ar′ is a substituted or unsubstituted pyridinyl group,wherein substituents of the pyridinyl group are a halogen atom, an alkylgroup, an alkoxy group, an aryl group, an aryloxy group, an aralkylgroup, an aralkyloxy group, an acyl group, a carboalkoxy group, acarboaryloxy group, a carboaralkyloxy group, a carboxyl group, a sulfogroup, a cyano group, a hydroxyl group, a nitro group, or an amino groupand has at least one hydrogen atom bound to the aforementioned group,and the biaryl compound is represented by the formula (3):Ar—Ar′  (3) wherein Ar and Ar′ are as defined above.
 2. The processaccording to claim 1, wherein the reaction is performed in the presenceof at least one species selected from the group consisting of thefollowing groups (A) and (B): (A) a Group Va element metal or a compoundthereof, a Group VIa element metal or a compound thereof, a Group VIIaelement metal or a compound thereof, and a Group VIIIa element metal ora compound thereof, (B) a Group Va element metal oxide, a Group VIaelement metal oxide, a Group VIIa element metal oxide and a Group VIIIaelement metal oxide obtained by reacting the metal or the metal compoundof the group (A) with hydrogen peroxide.
 3. The process for producing abiaryl compound according to claim 1, wherein hydrogen peroxide solutionin water is used.
 4. The process for producing a biaryl compoundaccording to claim 1, wherein the reaction is performed using hydrogenperoxide solution in water and in the presence of a quaternary ammoniumsalt or amine N-oxide.